| Post-translational modifications regulate protein expression,structure,localization,activity and function.ZNF281 is highly expressed in colorectal cancer,and promotes the proliferation,epithelial-mesenchymal transition and cancer stem cell maintenance.SUMOylation is a kind of ubiquitination-like modification.Ubc9 catalyzes the covalent binding of SUMO1 / 2 / 3 to the substrate protein(On the lysine residue in ψKXE motif).Whether ZNF281 has SUMOylation is still unknown.Objective: To study the relationship between ZNF281 and SUMOylation and the specific mechanism of recognition and removal of SUMOylation of ZNF281,and to further explore the effect of SUMOylation of ZNF281 on colorectal cancer.Methods: The expression levels of RNA and protein of ZNF281 and RNF4 in cancer and adjacent tissues,the relationship between genes and prognosis of cancer patients,and the correlation between genes were searched by GEPIA2,HPA and other online databases using bioinformatics method.A series of target vectors were constructed,and Western blot was used to detect the effects of the proteins regulating SUMOylation of ZNF281 on endogenous or exogenous sapylated modification.The interaction of ZNF281 with SUMO1-3 and SENP1 was detected by immunoprecipitation assay.Transwell was used to investigate the effect of ZNF281 on colorectal cancer cell migration.Conclusion: ZNF281 has mono-,di-and poly-SUMOylation,and is located in the cytoplasm,mainly at lysine residues K101,K128 and K225.The stability and transcriptional activity of ZNF281 were inhibited by SUMOylation,and the migration of colorectal cancer cells was inhibited.RNF4 recognizes SUMOylated ZNF281 through its SIM domain and promotes the stability of ZNF281.SENP1 promotes the de-SUMOylation and stability of ZNF281.Significance: This study provides a mechanism explanation and theoretical basis for RNF4,SENP1 and ZNF281 as diagnostic molecular markers and potential anticancer targets in colorectal cancer.Figure 30 Table 42 Reference 80... |
PDF Full Text Request